Trauma to neural tissue often leads to injury, dysfunction or death of cells and tissues, and thus to numerous adverse health conditions and disabilities. Such trauma includes damage to nerve cells, or to cells that support the healthy normal function and survival of nerve cells, and therefore includes damage to neural support cells, as well as to tissues that support the healthy, or normal, function and survival of nerve cells and tissues.
Injury to these cells and tissues typically occurs as a result of two factors. The first factor is the direct effect of the trauma itself. This is a primary type injury. The second factor results from biochemical cascades of cellular and metabolic processes that are activated or triggered directly by the trauma-induced tissue damage of the primary injury. The direct, or “primary,” damage (such as physical disruption) is not preventable. However, in accordance with the presently disclosed novel formulations, procedures and methods, the indirect damage, which is typically considered a “secondary injury”, or “secondary damage”, can be reduced, ameliorated or prevented by the present therapeutic treatment, intervention and formulations, and is therefore regarded as a salvageable neuropathology.
In the context of the presently disclosed technology the term “trauma” means a wound, injury or damage to a mammalian body or body part, or a condition resulting from such a wound or injury. In one aspect, the presently disclosed technology is particularly applicable to a wound, injury or damage that includes, as examples, physical, chemical, metabolic, medical, surgical or any other injury or damage to any nerve or nerve cell, neural support cell or neural support tissue, whether in the central nervous system or in the periphery, as described herein.
In another aspect, the presently disclosed technology is particularly applicable to physical trauma induced by, for example but not exclusively, vehicle accidents, workplace accidents, sports injuries and accidents, falls, burns, radiation, battlefield injuries such as but not exclusive to concussive blast injuries and injuries from landmines or improvised explosive devices (IED's), penetrating injuries and the like but can occur as a result of any traumatic event.
The presently disclosed technology is also particularly applicable to chemical trauma induced by, for example but not exclusively, medication or medication overdose, drug or drug overdose, drug abuse (such as methylenedioxyamphetamine, or MDMA, and the like), alcohol overdose, stimulant drugs such as pentylenetetrazol, streptozotocin, carbon dioxide poisoning, carbon monoxide poisoning, heavy metals, acrylamide and related chemicals, overexposure to certain environmental chemicals such as copper or natural hazards such as scorpion venom toxin, herbicides, agricultural insecticides such as lindane, hazardous industrial chemicals, neurotoxin bioterrorism chemicals such as soman and sarin, radiation bioterrorism chemicals such as polonium and strontium, and the like.
As an additional advantage, the presently disclosed technology is particularly applicable to metabolic trauma induced by, as examples but not exclusively, hypoxia, central nervous system ischemia, peripheral ischemia, enteric nervous system ischemia, hypoperfusion of nerve tissue, multiple sclerosis, shingles (herpes zoster), pathogens, diabetes, diabetic shock, stroke, epileptic or other seizure, post-polio syndrome, HIV/AIDS peripheral neuropathic pain, subacute posttraumatic myelopathy, and other effects, syndromes and conditions following some type of trauma to the body or its nervous system. Metabolic trauma can also include but is not exclusive to hypoglycemia, hyperglycemia, ischemia, diabetic shock, epilepsy or seizure, hypoperfusion of nerve tissue during cardiac arrest, hypoperfusion in newborns resulting from complications at delivery and the like.
The presently disclosed technology is similarly applicable to trauma induced by medical treatment or procedure, for example but not exclusively, injections, inoculation, implants, antibiotics, biologic drugs, antibodies, chemotherapy (for example but not exclusively with methotrexate, cisplatin, cytosine arabinose, carmustine, thiotepa among others), radiation therapy, immunosuppressants (for example tacrolimus), and the like, or during a medical procedure that can reduce or impede the blood supply for any period of time and the like.
Trauma from surgery includes, as examples, laparoscopy, amputation, mastectomy, cesarean section, cardiac surgery, hernia repair, cholecystectomy, joint replacement, thoracotomy, reparative surgery or any case, condition or situation where there is or might be detectable or undetectable cut, wound, injury or damage to nerves, nerve cells, neural support cells or neural support tissues or where long-term outcome from surgery can include adverse health conditions or disability as, for example, with failed back syndrome.
Trauma, or “neurotrauma”, to nerve cells, to neural support cells or to neural support tissues, can be, for example but not exclusively, traumatic brain injury (TBI), central nervous system ischemia, spinal cord injury, enteric nervous system injury, peripheral nerve injury or other type of injury to nerve cells.
Outcomes of traumatic damage to nerve cells or tissues differ significantly from the outcomes of traumatic damage to non-neural tissues and cells. Non-neural tissues repair relatively rapidly compared to nerves or nerve cells, and that repair often results in a damage site restored to nearly identical condition to the original (pre-trauma) state of the tissue, especially with respect to function. In stark contrast, trauma to neural tissue, such as nerves, nerve cells or any of the neural support cells or neural support tissues, often results in adverse health conditions or outcomes that persist for days, weeks or permanently. It is this set of disadvantageous characteristics and events regarding neural tissues to which the present invention is directed.
The severity and duration of such adverse outcomes resulting from neural tissue injury and cell death are governed by a balance of restorative, regenerative adaptive processes and destructive, degenerative maladaptive processes in those neural cells and tissues. In such injured cells and tissues, adaptive processes drive cells and tissues toward recovery and repair, and the restoration of pre-trauma function. During the same period, maladaptive processes drive cells and tissues toward loss of cell integrity and function, and even toward cell death. Effective control of the balance of adaptive and maladaptive processes following trauma to neural tissue has proven to be difficult. It is noteworthy that this balance is often skewed toward the maladaptive outcomes in neural tissue, such as cell or tissue death, and thus to permanent dysfunction and disability. Conventional medical and therapeutic systems and processes have shown little effectiveness in addressing these negative outcomes. There is therefore a significant clinical and societal need for new methods and formulations directed toward the treatment of secondary injury to neural tissues, such as nerve cells, neural support cells and neural support tissues that maintain the health and function of nerve cells. The scope and spirit of the many present invention embodiments are directed toward addressing this clinical and societal heretofore unsolved need by promoting natural adaptive processes while inhibiting intrinsic maladaptive processes, thereby reducing or preventing the development, or the risk of development, of neuropathology as a result of traumatic injury.
The present embodiments of the invention include, among other advantageous aspects, numerous formulations adapted and arranged for administration to a subject or patient in need thereof soon after that subject or patient has experienced a traumatic event. In another key aspect, some particular disclosed embodiments include formulations that may be used in preventative ways, such as when a traumatic event is likely, anticipated or possible. In a similar manner, some particular disclosed embodiments include formulations that may be used in prophylactic ways, such as in the case of a procedure about which incidence studies inform may lead to neuropathology.
In one significant aspect, the disclosed formulations comprise two or more pharmaceutically effective compounds, administered to a subject or patient in accordance with the pharmaceutical effectiveness of the components and amounts to be administered. In some embodiments, the relative timing of the administrations of the formulations is keyed to the context of the actual, possible or likely nature of the injury. Regarding the timing aspects, the embodiments of the invention can be practiced with respect to the time that the injury or disorder has occurred, or with respect to a possibility, a probability or a likelihood that an injury will occur in the impending future. Thus, in one aspect some embodiments can be adapted and arranged to preventive purposes or to prophylactic purposes or to curative purposes or to ameliorative purposes.
Embodiments of the invention can therefore be practiced within a rationalized earliest possible time frame following, or preceding, trauma, thereby to promote adaptive processes and to inhibit maladaptive processes activated by the trauma, or which are likely to be activated by the trauma. Thus, the present formulations, methods, and procedures are all directed toward reducing or preventing the development, or the risk of development, of secondary nerve cell damage, loss of function, or cell death.
In this same vein, the presently disclosed invention and its many embodiments address the critical facts that damage or injury to nerves, nerve cells, neural support cells and neural support tissues can be a result of trauma, but such damage or injury can also be secondary, due to a complex series of events or mechanisms often triggered by the direct injury. Disability arising from the primary injury occurring at the moment of the traumatic event, whether it is to brain, spinal cord, enteric nervous system or peripheral nervous system, is not preventable. However, disability resulting from such secondary injury is somewhat or completely preventable in the context of the invention. This prevention or amelioration is the object of the many presently disclosed invention embodiments. The presently disclosed invention and its embodiments comprise an intervention with a pharmaceutically appropriate additive or synergistic drug combination, given following trauma or in advance of expected or potential trauma, and administered by a route that provides access under the circumstances of the traumatic event. The scope and the spirit of the many presently disclosed embodiments of the technology are thus directed to promoting the naturally-occurring adaptive processes triggered by, and resulting from, the primary damage and to inhibit the naturally-occurring maladaptive processes triggered by the primary damage. Thus, the formulations, methods and procedures of the presently disclosed technology will reduce or prevent the development, or the risk of development, of neuropathology as a result of traumatic injury.